In this study the effects of various nephrotoxins (e.g., organic solvents, heavy metals, antibiotics) and certain experimental manipulations will be examined for their effects on renal and non-renal transport processes. With the nephrotoxins an attempt will be made to determine whether or not the action is a direct one. Routine histological procedures will be employed to monitor the onset of the nephrotoxicity. For functional studies, mainly in vitro procedures will be used with the toxins administered to the animals (rats, rabbits, guinea pigs) prior to the experiments as well as added directly to renal slice or homogenate preparations. Renal slices will be tested for their ability to reaccumulate inorganic electrolytes after leaching and to maintain a normal electrolyte distribution and tissue water content after exposure to nephrotoxins. Renal slice uptake or organic acids (e.g., p-aminohippurate) and organic bases (e.g. tetraethylammonium) will be studied. The relative contribution of decreased renal blood flow to the damage of specific transport processes will be assessed by producing both acute and chronic periods of renal artery occlusion, after which renal slice transport studies will be done. The importance of metabolism of the nephrotoxin in the production of its action will be studied using agents that potentially enhance or decrease nephrotoxin metabolism, e.g. phenobarbital pretreatment, SKF-525A. Finally an attempt will be made to determine the subcellular distribution of nephrotoxic agents. This will involve standard fractionation technics and may help develop a better understanding of mechanisms of action through finding potential sites of action. A variety of factors that affect the transport of radiopaque substances will be studied. Species differences and temperature effects on slice uptake and runout will be examined. Also the subcellular distribution of these iodinated organic acids and their metabolites will be measured.